Human cancer vaccines

人类癌症疫苗

• 批准号: 12213116
• 负责人: SATO Noriyuki
• 金额: $ 32.19万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12213116/
• 关键词: tumor antigens; peptide vaccines; CTL; clinical trials; autologous tumor; Bioinformatics; survivin; SYT-SSX; 癌ワクチン; 癌抗原ペプチド; 胃癌抗原遺伝子; 骨肉腫抗原遺伝子; HLA-A24; PBF; 肉腫; 臨床試験; 癌免疫; 癌抗原処理提示; 抗原ペプチド; hsc 70; 分子シャペロン; ヒト癌抗原; リカバリン; HLA-DR8

Three research projects were successfully studied. 1) We identified human osteosarcoma antigen PBF, papilloma-binding factor, from autologous CTL and osteosarcoma OS2000 line. PBF was expressed in a large part of soft part tumors as well as approximately 50 % tumors of epithelial origins, whereas it was not detected in normal part of tissues particularly in the protein level. These observations suggest that PBF could be utilized in the immunotherapy of cancers. 2) Reverse-immunological approaches of tumor antigens indicated that survivin could work as the tumor antigens. Particularly, survivin-derived 2Bpeptide induced CTL in many cancer patients in the HLA-A24 restricted manner. We are now underway the phase I clinical trials of this peptide in colon, breast, lung cancers, indicating that there are no adverse effects. Some of these patients demonstrated certain clinical responses such as reduction in tumor size in CT as well as in tumor marker levels. We are also underway the phase I clinical trials of HLA-A24-restricted B peptide derived from the SYT-SSX chromosomal translocation fusion product in synovial sarcoma patients. In this trial, there are no adverse effects, and two out of six patients indicated an increasing number of tetramer-positive CTL precursors. 3) We identified 35 novel tumor antigens by bioinformatics in silico approaches. Wet studies by using RT-PCR analysis confirmed that 7 out of 35 antigens have strict expression profiles as the tumor antigens.

三个研究项目研究成功。 1) 我们从自体 CTL 和骨肉瘤 OS2000 系中鉴定出人骨肉瘤抗原 PBF、乳头状瘤结合因子。 PBF在大部分软组织肿瘤以及大约50%的上皮来源肿瘤中表达，而在正常组织部分中未检测到，特别是在蛋白质水平上。这些观察结果表明 PBF 可用于癌症的免疫治疗。 2)肿瘤抗原的反向免疫学方法表明survivin可以作为肿瘤抗原。特别是，生存素衍生的2B肽以HLA-A24限制的方式在许多癌症患者中诱导CTL。我们现在正在进行这种肽在结肠癌、乳腺癌、肺癌中的I期临床试验，表明没有不良反应。其中一些患者表现出某些临床反应，例如 CT 中肿瘤大小以及肿瘤标志物水平的减小。我们还正在进行来自SYT-SSX染色体易位融合产物的HLA-A24限制性B肽在滑膜肉瘤患者中的I期临床试验。在这项试验中，没有出现任何不良反应，六分之二的患者表明四聚体阳性 CTL 前体的数量不断增加。 3) 我们通过计算机生物信息学方法鉴定了 35 种新型肿瘤抗原。使用 RT-PCR 分析的湿法研究证实，35 种抗原中有 7 种具有严格的肿瘤抗原表达谱。

项目成果

佐藤昇志,矢田純一,奥村康: "中外医学社"Annual Review免疫2000. 354 (2000)

Noboru Sato、Junichi Yada、Yasushi Okumura：“中外医学社”免疫学年度评论 2000. 354 (2000)

Ida, K., Sato, N., et al.: "Improved induction of synovial sarcoma-reactive CTLs by SYT-SSX junction peptide/HLA-A*2402 complex anchor substitution."J.Immunol.. in press.

Ida, K.、Sato, N. 等人：“通过 SYT-SSX 连接肽/HLA-A*2402 复合物锚替代改善滑膜肉瘤反应性 CTL 的诱导。”J.Immunol.. 正在出版。

Takamura, Y., Ikeda, H., Sato, N., et al.: "Regulation of MHC class II expression in glioma cells by class II transactivator (C II TA)."Glia. 45. 392-405 (2004)

Takamura, Y.、Ikeda, H.、Sato, N. 等人：“II 类反式激活因子 (C II TA) 对神经胶质瘤细胞中 MHC II 类表达的调节”。

Hirohashi, Y., et al.: "An HLA-A24-restricted CTL epitope of a tumor asscoated protein, survivin"Clin. Cancer Res.. 8. 1731-1739 (2002)

Hirohashi, Y., et al.：“肿瘤相关蛋白存活蛋白的 HLA-A24 限制性 CTL 表位”Clin。

Histone deacetylation, but not hypermethylation, modifies CIITA and MHC calss II gene expression in squamous cell carcinomas.

组蛋白脱乙酰化而非高甲基化会改变鳞状细胞癌中 CIITA 和 MHC calss II 基因的表达。

• 发表时间: 2003
• 期刊: J.Immunol. 170
• 作者: Kanaseki;T.;Ikeda;H.;Takamura;Y.;Toyota;M.;Hirohashi;Y.;Tokino;T.;Himi;T.;Sato;N.
• 通讯作者: N.